Borrowing hydrogen: A catalytic route to C-C bond formation from alcohols

Article abstract of DOI:10.1039/b312162c

Ruthenium complexes have been shown to perform efficient transfer hydrogenation reactions between alcohols and alkenes; in combination with an in situ Wittig reaction, indirect formation of C-C bonds has been achieved from alcohols.

Full text of DOI:10.1039/b312162c

Borrowing hydrogen: a catalytic route to C–C bond formation from
alcohols†
Michael G. Edwards,a Rodolphe F. R. Jazzar,a Belinda M. Paine,a Duncan J. Shermer,a Michael K.
Whittlesey,*a Jonathan M. J. Williams*a and Dean D. Edneyb
a Department of Chemistry, University of Bath, Claverton Down, Bath, UK BA2 7AY.
E-mail: chsmkw@bath.ac.uk. E-mail: chsjmjw@bath.ac.uk
b GlaxoSmithKline Research & Development, Old Powder Mills, Tonbridge, Kent, UK TN11 9AN
Received (in Cambridge, UK) 1st October 2003, Accepted 24th October 2003
First published as an Advance Article on the web 18th November 2003
Ruthenium complexes have been shown to perform efficient
transfer hydrogenation reactions between alcohols and alkenes;
in combination with an in situ Wittig reaction, indirect
formation of C–C bonds has been achieved from alcohols.
reforms the starting dihydride upon reaction with H2. The rapid
hydrogenation of alkenes5 and the reversibility of the pathway
illustrated in Scheme 2 prompted us to investigate the suitability of
alcohols as hydrogen donors in this process.6
It was subsequently demonstrated that vinyltrimethylsilane (3)
could be completely hydrogenated by complex 1 at 70 °C to provide
ethyltrimethylsilane (4) with isopropanol acting as the hydrogen
donor (Scheme 3). Indeed, the crossover transfer hydrogenation7
reaction between one equivalent of alcohol and one equivalent of
alkene could also be readily achieved (Scheme 3). (±)-Phenethyl
alcohol (6) and tert-butyl cinnamate (5) were converted solely into
acetophenone (8) and tert-butyl dihydrocinnamate (7) using 5
mol% of complex 1.
The ability to effect a crossover transfer hydrogenation is critical
to the success of the indirect Wittig reaction identified in Scheme 1.
In the absence of crossover hydrogenation the cycle is unable to
proceed once the initial catalyst has been exhausted. Following the
success of these transfer hydrogenation reactions the catalytic
activity of complex 1 in the indirect Wittig process was examined
(Scheme 4, Table 1). Table 1 shows the performance of complex 1
(5 mol% loading) for reaction of benzyl alcohol (9) with the ester
The concept of catalytic electronic activation as a route to new C–C
bond forming reactions is an attractive one since it allows the use of
alcohols as substrates.1 One model for this involves the indirect
Wittig reaction of a temporarily oxidized alcohol (Scheme 1) to
yield an alkene, which is then reduced to give the final longer chain
alkane.2 The key to the catalytic cycle is the borrowing of
hydrogen—dehydrogenation of alcohol to aldehyde releases H2,
which would be stored by the catalytic metal fragment and then
returned in the final hydrogenation step. The development of
catalytic systems is therefore likely to involve metal complexes in
which H2 dissociation and re-coordination is facile, preferably
without the requirement for forcing conditions.3
Our previous attempts at achieving this reaction using an
iridium-based system required heating at 150 °C for 72 h.2 Herein
we report on a ruthenium-catalysed approach requiring milder
reaction conditions. The use of a ruthenium N-heterocyclic carbene
complex allows the reaction to be carried out at significantly lower
temperatures and reaction times. We have recently reported the
facile C–H bond activation of the N-heterocyclic carbene
1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) in Ru(I-
Mes)(PPh3)2(CO)H2 (1) at room temperature in the presence of a
sacrificial alkene (Scheme 2).4 The C–H cleavage product 2 readily
Scheme 3 Transfer hydrogenation reactions with complex 1.
Scheme 4 Ruthenium catalysed indirect Wittig reactions with benzyl ester
ylide 10.
Scheme 1 Catalytic electronic activation: indirect Wittig reaction upon
alcohols.
Table 1 Effect of ruthenium catalysts upon the indirect Wittig reaction of
benzyl alcohol 9a
Ligand
(mol%)
Conversion
(%)b
Entry
Precursor (5 mol%)
1
2
3
4c
1
—
—
IMes (5)
IMes (5)
90
80
87
86
Ru(PPh3)3(CO)H2
Ru(PPh3)3(CO)H2
Ru(PPh3)3(CO)H2
Scheme 2 Reversible dehydrogenation/hydrogenation pathway of complex
1.
a The reactions were carried out on a 0.5 mmol scale in toluene (1.5 mL) at
† Electronic Supplementary Information (ESI) available: Experimental
procedures and characterization data for compounds 1, 11, 12, 13, 15 and 17
along with general experimental procedures. See http://www.rsc.org/
suppdata/cc/b3/b312162c/
1
80 °C for 24 hours using 1.1 equivalents of ylide 10. b Determined by H
NMR spectroscopy. c The precursor and IMes were heated at 70 °C for 1.5
hours in toluene before addition of the remaining reagents.
90
C h e m . C o m m u n . , 2 0 0 4 , 9 0 – 9 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

ylide (10) in toluene solution at 80 °C. In all cases 5 mol% of
vinyltrimethylsilane (3) was added to accomplish the initial
dehydrogenation of the catalyst required for the reaction to proceed.
The reaction catalysed by complex 1 afforded 90% of the
dihydrocinnamate product (11) after 24 hours (entry 1). The
complex Ru(PPh3)3(CO)H2 also proved to be successful in the
indirect Wittig reaction, although it proved to be inferior to
complex 1 over the same reaction period (entry 2).8
The highest levels of activity of complex 1 are associated with
isolated material; however in situ generation of the catalyst proved
to be successful (entries 3 and 4). Thus, whilst the carbene complex
1 is the most successful catalyst, commercially available complex
Ru(PPh3)3(CO)H2 was also reasonably effective.
addition, the results indicate that the presence of an N-heterocyclic
carbene ligand is beneficial for improved reactivity in comparison
with other complexes.
In conclusion, we have demonstrated that ruthenium complexes
act as catalysts for the formation of C–C bonds from alcohol
substrates via an intriguing indirect Wittig reaction.
We thank the EPSRC, GlaxoSmithKline and the University of
Bath for financial support and Johnson Matthey plc for the loan of
ruthenium trichloride.
Notes and references
1 P. J. Black, W. Harris and J. M. J. Williams, Angew. Chem., Int. Ed.,
2001, 40, 4475.
We further demonstrated that the indirect Wittig reaction
catalysed by 1 could be successfully achieved in high yield by the
use of alternative phosphorane ester ylides with other alcohol
substrates (Scheme 5). Using optimised reaction conditions (1
mol% 1, 1.00 M concentration, 80 °C) the indirect Wittig adducts
11, 12, 13, 15 and 17 were obtained in good to excellent isolated
yields following column chromatography (70–84%). These results
demonstrate that complex 1 displays high catalytic activity for C–C
bond formation via this route at moderately low temperatures (80
°C). In contrast, the previously reported2 iridium catalysed
reactions afforded indirect Wittig adducts in lower yield, 47–71%,
even under extremely forcing reaction conditions (150 °C, 72
hours) and at considerably higher catalyst loadings (5 mol%). In
2 M. G. Edwards and J. M. J. Williams, Angew. Chem., Int. Ed., 2002, 41,
4740.
3 J. E. Bäckvall, J. Organomet. Chem., 2002, 652, 105.
4 R. F. R. Jazzar, S. A. Macgregor, M. F. Mahon, S. P. Richards and M. K.
Whittlesey, J. Am. Chem. Soc., 2002, 124, 4944.
5 Several hydrogenation reactions using hydrogen gas have been reported
for NHC complexes. See for example: H. M. Lee, D. C. Smith Jr., Z. He,
E. D. Stevens, C. S. Yi and S. P. Nolan, Organometallics, 2001, 20, 794;
H. M. Lee, T. Jiang, E. D. Stevens and S. P. Nolan, Organometallics,
2001, 20, 1255; M. T. Powell, D.-R. Hou, M. C. Perry, X. Cui and K.
Burgess, J. Am. Chem. Soc., 2001, 123, 8878; L. D. Vázquez-Serrano, B.
T. Owens and J. M. Buriak, Chem. Commun., 2002, 2518; M. C. Perry,
X. Cui, M. T. Powell, D.-R. Hou, J. H. Riebenspies and K. Burgess, J.
Am. Chem. Soc., 2003, 125, 113.
6 Transfer hydrogenation reactions have been reported with a range of
transition metal NHC complexes: A. C. Hillier, H. M. Lee, E. D. Stevens
and S. P. Nolan, Organometallics, 2001, 20, 4246; J. Louie, C. W.
Bielawski and R. H. Grubbs, J. Am. Chem. Soc., 2001, 123, 11312; M. A.
Albrecht, J. R. Miecznikowski, A. Samuel, J. W. Faller and R. H.
Crabtree, Organometallics, 2002, 21, 3596; A. A. Danopoulos, S.
Winston and W. B. Motherwell, Chem. Commun., 2002, 1376; M. A.
Albrecht, R. H. Crabtree, J. A. Mata and E. Peris, Chem. Commun., 2002,
32; M. Poyatos, J. A. Mata, E. Falomir, R. H. Crabtree and E. Peris,
Organometallics, 2003, 22, 1110; M. Poyatos, E. Mas-Marzá, J. A. Mata,
M. Sanaú and E. Peris, Eur. J. Inorg. Chem., 2003, 1215.
7 The literature contains very few reports of stoichiometric crossover
transfer hydrogenation reactions between alcohols and alkenes. A few
examples of crossover transfer hydrogenation using a small excess of
alkene acceptor have been reported. See for example: M. E. Krafft and B.
Zorc, J. Org. Chem., 1986, 51, 5482.
8 Ru(PPh3)3(CO)H2 has been reported as catalysing hydrogenation of
alkenes, aldehydes and ketones, although very forcing conditions are
required for substrates with CNO groups. F. Kakiuchi, S. Sekine, Y.
Tanaka, A. Kamatani, M. Sonoda, N. Chatani and S. Murai, Bull. Chem.
Soc. Jpn., 1995, 68, 62; R. A. Sanchez-Delgado and O. L. de Ochoa, J.
Organomet. Chem., 1980, 202, 427; R. A. Sanchez-Delgado, A.
Andriollo, O. L. de Ochoa, T. Suarez and N. Valencia, J. Organomet.
Chem., 1981, 209, 77; G. Speier and L. Marko, J. Organomet. Chem.,
1981, 210, 253.
Scheme 5 Synthesis of indirect Wittig reaction adducts (1 mol% 1, 1.1
equiv. Ph3PNCHCO2R, 2 mol% H2CNCHSiMe3, PhMe, 1.00 M, 80 °C); (a)
24 hour reaction time; (b) 48 hour reaction time.
C h e m . C o m m u n . , 2 0 0 4 , 9 0 – 9 1
91